The essential role of MALT1 (mucosa associated lymphoid tissue lymphoma translocation protein 1) in influencing immune responses is described in numerous publications. For example, Rudi Beyaert et al. (WO 2009/065897) describe certain compounds as inhibitors of MALT1 proteolytic and/or autoproteolytic activity.
Studies in BCL10 and MALT 1 deficient mice seem to suggest their essential role in the signaling cascade from the antigen receptors to the transcription factor NFkB. Moreover chromosomal translocations leading to overexpression of BCL10 and MALT 1, or creating the constitutively active fusion protein API2-MALT1, appear to yield in an uncontrolled and stimulus-independent activation of NFkB. Inhibitors of the proteolytic activity of MALT1 have been described with activity in preclinical lymphoma models (Vincendeau et al. Int. J. Hematol. Oncol. 2013, 2, 409).
Moreover, certain publications appear to suggest the important role of MALT1 and its proteolytic function in signaling cascades triggered by innate cell receptors like Dectin receptors and in signaling cascades triggered by G-protein coupled receptors in many cell types.
Consequently, there appears to be a desire to discover and develop potent MALT1 inhibitors comprising valuable pharmacological properties.